dbSNP rs113716376: LINGO1:p.Asp610Asp (chr15-77614077-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_032808.7(LINGO1):c.1830C>T(p.Asp610Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,610,260 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 18 hom., cov: 33)

Exomes 𝑓: 0.00094 ( 20 hom. )

Consequence

LINGO1
NM_032808.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.06

Publications

2 publications found

Variant links:

Genes affected

LINGO1 (HGNC:21205): (leucine rich repeat and Ig domain containing 1) Predicted to enable epidermal growth factor receptor binding activity. Predicted to act upstream of or within generation of neurons and protein kinase B signaling. Predicted to be located in plasma membrane. Predicted to be active in extracellular matrix and extracellular space. Implicated in autosomal recessive non-syndromic intellectual disability and glaucoma. [provided by Alliance of Genome Resources, Apr 2022]

LINGO1 Gene-Disease associations (from GenCC):

intellectual disability, autosomal recessive 64
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

LINGO1 links:

LOC105370906 (HGNC:):

LOC105370906 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 15-77614077-G-A is Benign according to our data. Variant chr15-77614077-G-A is described in ClinVar as Benign. ClinVar VariationId is 779902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.07 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00798 (1215/152304) while in subpopulation AFR AF = 0.0268 (1114/41564). AF 95% confidence interval is 0.0255. There are 18 homozygotes in GnomAd4. There are 586 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 Unknown,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO1	NM_032808.7 link	c.1830C>T	p.Asp610Asp	synonymous_variant	Exon 2 of 2	ENST00000355300.7	NP_116197.4	Q96FE5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO1	ENST00000355300.7 link	c.1830C>T	p.Asp610Asp	synonymous_variant	Exon 2 of 2	1	NM_032808.7	ENSP00000347451.6		Q96FE5-1
LINGO1	ENST00000561030.5 link	c.1812C>T	p.Asp604Asp	synonymous_variant	Exon 4 of 4	1		ENSP00000453853.1		Q96FE5-2

Frequencies

GnomAD3 genomes

AF:

0.00798

AC:

1214

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0269

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00451

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00218

AC:

522

AN:

239226

AF XY:

0.00180

show subpopulations

Gnomad AFR exome

AF:

0.0295

Gnomad AMR exome

AF:

0.00161

Gnomad ASJ exome

AF:

0.000203

Gnomad EAS exome

AF:

0.0000579

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000234

Gnomad OTH exome

AF:

0.000852

GnomAD4 exome

AF:

0.000942

AC:

1373

AN:

1457956

Hom.:

Cov.:

AF XY:

0.000862

AC XY:

625

AN XY:

724986

show subpopulations

African (AFR)

AF:

0.0277

AC:

925

AN:

33386

American (AMR)

AF:

0.00176

AC:

AN:

43812

Ashkenazi Jewish (ASJ)

AF:

0.000307

AC:

AN:

26044

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39530

South Asian (SAS)

AF:

0.0000699

AC:

AN:

85890

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53188

Middle Eastern (MID)

AF:

0.00226

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000186

AC:

206

AN:

1110074

Other (OTH)

AF:

0.00227

AC:

137

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

164

245

327

409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00798

AC:

1215

AN:

152304

Hom.:

Cov.:

AF XY:

0.00787

AC XY:

586

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0268

AC:

1114

AN:

41564

American (AMR)

AF:

0.00451

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68020

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

121

182

242

303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00508

Hom.:

Bravo

AF:

0.00948

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.1

(source)

DANN

Benign

0.81

PhyloP100

-1.1

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over